Changes in DNA methylation are associated with the development of drug resistance in cervical cancer cells

Chih Cheng Chen, Kuan Der Lee, Mei Yu Pai, Pei Yi Chu, Chia Chen Hsu, Chia Chen Chiu, Li Tzong Chen, Jang Yang Chang, Shu Huei Hsiao, Yu Wei Leu

研究成果: 雜誌貢獻文章

27 引文 斯高帕斯(Scopus)

摘要

Background and propose: Changes in DNA methylation are associated with changes in somatic cell fate without the alteration of coding sequences. In addition to its use as a traceable biomarker, reversible DNA methylation could also serve as a therapeutic target. In particular, if the development of drug resistance is associated with changes in DNA methylation, then demethylation might reverse the resistance phenotype. The reversion of the drug-resistance might then be feasible if the association between abnormal DNA methylation and the development of drug-resistance could be identified. Methods: Methylation differences between the drug-resistance cervical cancer cell, SiHa, and its derived oxaliplatinresistant S3 cells were detected by methylation specific microarray. The drug-resistance cells were treated with demethylation agent to see if the resistance phenotype were reversed. Targeted methylation of one of the identified locus in normal cell is expected to recapitulate the development of resistance and a two-component reporter system is adopted to monitor the increase of DNA methylation in live cells. Results: In this report, we identified methylation changes, both genome-wide and within individual loci, in the oxaliplatin-resistant cervical cancer cell S3 compared with its parental cell line SiHa. Treatment of S3 with a demethylation agent reversed increases in methylation and allowed the expression of methylation-silenced genes. Treatment with the demethylation agent also restored the sensitivity of S3 to cisplatin, taxol, and oxaliplatin to the same level as that of SiHa. Finally, we found that methylation of the target gene Casp8AP2 is sufficient to increase drug resistance in different cells. Conclusions: These results suggest that global methylation is associated with the development of drug resistance and could serve as a biomarker and therapeutic target for drug resistance in cervical cancer.
原文英語
文章編號98
期刊Cancer Cell International
15
發行號1
DOIs
出版狀態已發佈 - 十月 13 2015
對外發佈Yes

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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    Chen, C. C., Lee, K. D., Pai, M. Y., Chu, P. Y., Hsu, C. C., Chiu, C. C., Chen, L. T., Chang, J. Y., Hsiao, S. H., & Leu, Y. W. (2015). Changes in DNA methylation are associated with the development of drug resistance in cervical cancer cells. Cancer Cell International, 15(1), [98]. https://doi.org/10.1186/s12935-015-0248-3